Procedure Volume and the Association with Short-term Mortality Following Abdominal Aortic Aneurysm Repair in European Populations: A Systematic Review

Objective: To evaluate the relationship between the volume of abdominal aortic aneurysm (AAA) procedures undertaken and the primary outcome of mortality in Europe. Previous systematic reviews of this relationship are outdated and are overwhelmingly based on US data. Data sources: Comprehensive searching within MEDLINE and other bibliographic databases supplemented by citation searching and hand-searching of journals was undertaken to identify studies that reported the effect of hospital or clinician volume on any reported outcomes in adult, European populations, undergoing AAA repair and published in the last 10 years. Methods: Two reviewers conducted study selection with independent, duplicate data extraction and quality assessment. A planned meta-analysis was not conducted because of the high risk of bias, the likelihood of individual study subjects being included in more than one study and diversity in the clinical populations studied and methods used. Results: Sixteen studies (n = 237,074 participants) from the UK (n = 11 studies), Germany (n = 3 studies), Norway (n = 1 study), and one from the UK and Sweden were included. Data in the included studies came from administrative databases and clinical registries incorporating a variety of clinical and procedural groups; the study quality was limited by the use of observational study designs. Overall, the evidence favoured the existence of an inverse volume outcome relationship between hospital volume and mortality. Insufficient evidence was available to reach conclusions on the relationship between clinician volume and outcome and between hospital or clinician volume and secondary outcomes including complications and length of hospital stay. Conclusions: The evidence from this review suggests a relationship between the hospital volume of AAA procedures conducted and short-term mortality; however, as volume typically represents a complex amalgamation of factors further research will be useful to identify the core characteristics of volume that influence improved outcomes

Diagnostic accuracy of the aortic dissection detection risk score alone or with D-dimer for acute aortic syndromes: systematic review and meta-analysis

Objectives To evaluate the diagnostic accuracy of the aortic dissection detection risk score (ADD-RS) used alone or in combination with D-dimer for detecting acute aortic syndrome (AAS) in patients presenting with symptoms suggestive of AAS. Methods We searched MEDLINE, EMBASE, and the Cochrane Library from inception to February 2024. Additionally, the reference lists of included studies and other systematic reviews were thoroughly searched. All diagnostic accuracy studies that assessed the use of ADD-RS alone or with D-Dimer for diagnosing AAS compared with a reference standard test (e.g. computer tomographic angiography (CTA), ECG-gated CTA, echocardiography, magnetic resonance angiography, operation, or autopsy) were included. Two reviewers independently selected and extracted data. Risk of bias was appraised using QUADAS-2 tool. Data were synthesised using hierarchical meta-analysis models. Results We selected 13 studies from the 2017 citations identified, including six studies evaluating combinations of ADD-RS alongside D-dimer>500ng/L. Summary sensitivities and specificities (95% credible interval) were: ADD-RS>0 94.6% (90%, 97.5%) and 34.7% (20.7%, 51.2%), ADD-RS>1 43.4% (31.2%, 57.1%) and 89.3% (80.4%, 94.8%); ADD RS>0 or D-Dimer>500ng/L 99.8% (98.7%, 100%) and 21.8% (12.1%, 32.6%); ADD RS>1 or D-Dimer>500ng/L 98.3% (94.9%, 99.5%) and 51.4% (38.7%, 64.1%); ADD RS>1 or ADD RS = 1 with D-dimer>500ng/L 93.1% (87.1%, 96.3%) and 67.1% (54.4%, 77.7%). Conclusions Combinations of ADD-RS and D-dimer can be used to select patients with suspected AAS for imaging with a range of trade-offs between sensitivity (93.1% to 99.8%) and specificity (21.8% to 67.1%)

Patient-reported outcome measures in patients with peripheral artery disease: Protocol for a systematic review

Peripheral arterial disease (PAD) results in reduced health-related quality of life and significant functional impairment. Patient-reported outcome measures (PROMs) are important when considering the impact of treatments and management strategies in patients with PAD. A variety of studies have reported the use of different PROMs in patients with PAD. However, PROMs should provide valid and reliable findings to help in healthcare decision-making. The aim of this proposed systematic review is to comprehensively evaluate the psychometric properties of PROMs developed and/ or validated in patients with PAD

Patient reported out come measures in patients with abdominal a ortic a neurysms: a systematic review p rotocol

Background: Abdominal aortic aneurysm (AAA) is a dilatation of the abdominal aorta, which is usually asymptomatic. However, rupture of the aneurysm can be fatal or require complex surgery with potential complications, leading to a poor quality of life. Patient reported outcome measures (PROMs) are becoming increasing ly important in the current era of healthcare management. PROMs are used to directly assess how patients feel or function in relation to their health condition without any interpretation . Generic, disease - specific and preference - based PROMs ca n be used to assess the quality of life (QoL), symptoms and functional limitations in patients with AAA including those under surveillance or undergoing endovascular or open surgery or screening . However, these tools vary in terms of their reliability, validity and suitability for use in patients with AAA in a clinical setting. Objectives: To identify, summarise and assess PROMs that have been administered to patients with a diagnosis of AAA including those under surveillance or undergoing endovascular or open surgery or screening . Methods: Key electronic databases and research registers will be searched including: MEDLINE and MEDLINE in Process, EMBASE, PsycINFO, PROQOLID, CINAH L, PROMS Bibliography (Oxford University), Web of Science and the Cochrane Library databases from inception. A two - stage search approach will be used. The first stage will utilise general terms for PROMs to identify studies. These will be retrieved and t he title and abstract will be examined for additional PROM terms. Stage 2 will incorporate these terms with the preliminary search strategy and a methodological search filter . Searches will be supplemented by hand - searching reference lists of relevant reviews and included studies. Study selection, data extraction and quality assessment will be performed independently by at least 2 reviewers. All English language instruments identified as PROMs for patients with AAA will be included. Data will be extracted regarding type of PROM, methods and results. Methodological quality of included studies will be assessed using the CO nsensus - based S tandards for the selection of health st atus Measurement IN struments checklist (COSMIN) and the psychometric properties of the PROMs will be assessed on criteria bas ed in published recommendations. Findings will be presented as narrative and tabular summaries. Discussion : This systematic review will identify PROMs that are used to assess QoL , symptoms and functional limitations in patients with AAA and assess their effectiveness for this population and application to clinical practice. The findings of the review will help inform a project examining the re-configuration of vascular services in the UK, and identify targets for future research

Cervical spine immobilisation following blunt trauma in pre-hospital and emergency care: a systematic review

Objectives To assess whether different cervical spine immobilisation strategies (full immobilisation, movement minimisation or no immobilisation), impact neurological and/or other outcomes for patients with suspected cervical spinal injury in the pre-hospital and emergency department setting. Design Systematic review following Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Data sources MEDLINE, EMBASE, CINAHL, Cochrane Library and two research registers were searched until September 2023. Eligibility criteria All comparative studies (prospective or retrospective) that examined the potential benefits and/or harms of immobilisation practices during pre-hospital and emergency care of patients with a potential cervical spine injury (pre-imaging) following blunt trauma. Data extraction and synthesis Two authors independently selected and extracted data. Risk of bias was appraised using the Cochrane ROBINS-I tool for non-randomised studies. Data were synthesised without meta-analysis. Results Six observational studies met the inclusion criteria. The methodological quality was variable, with most studies having serious or critical risk of bias. The effect of cervical spine immobilisation practices such as full immobilisation or movement minimisation during pre-hospital and emergency care did not show clear evidence of benefit for the prevention of neurological deterioration, spinal injuries and death compared with no immobilisation. However, increased pain, discomfort and anatomical complications were associated with collar application during immobilisation. Conclusions Despite the limited evidence, weak designs and limited generalisability, the available data suggest that pre-hospital cervical spine immobilisation (full immobilisation or movement minimisation) was of uncertain value due to the lack of demonstrable benefit and may lead to potential complications and adverse outcomes. High-quality randomised comparative studies are required to address this important question

Interventions to promote oral nutritional behaviours in people living with neurodegenerative disorders of the motor system : a systematic review

Background & Aims: Weight loss is common in people with neurodegenerative diseases of the motor system (NDMS), such as Parkinson’s disease and Amyotrophic Lateral Sclerosis, and is associated with reduced quality of life, functional ability and survival. This systematic review aims to identify interventions and intervention components (i.e. behaviour change techniques [BCTs] and modes of delivery [MoDs]) that are associated with increased effectiveness in promoting oral nutritional behaviours that help people with NDMS to achieve a high-calorie diet. Methods: Eight electronic databases including MEDLINE and CINAHL were searched from inception to May 2018. All interventions from included studies were coded for relevant BCTs and MoDs. Methodological quality of studies was assessed using the Cochrane risk of bias tool. Results: Fourteen studies were included. Of these, eight studies reported interventions to assist with swallowing difficulties and six studies reported interventions targeting dietary content. Beneficial effects in managing swallowing difficulties were observed with video assisted swallowing therapy, lung volume recruitment and swallowing management clinics with outpatient support. In contrast, studies reporting effectiveness of chin down posture, use of thickened liquids and respiratory muscle training were inconclusive. Positive effects in interventions targeting dietary content included the use of food pyramid tools, individualised nutritional advice with nutritional interventions, electronic health applications, face-to-face dietary counselling and high fat, high carbohydrate and milk whey protein supplements. Individualised nutritional advice with weekly phone contact did not appear to be effective. Most frequently coded BCTs were ‘instructions on how to perform the behaviour’, ‘self-monitoring’ and ‘behavioural practice/rehearsal’. Most commonly identified MoDs were ‘human’, ‘face-to-face’ and ‘somatic therapy’. However, the robustness of these findings are low due to small number of studies, small sample sizes and large between-study variability. Conclusions: Despite the limited evidence, these findings may help inform the development of more effective interventions to promote oral nutritional behaviours in people with NDMS. However, further research is needed to demonstrate which interventions, or intervention components, yield most benefit

Vedolizumab for the Treatment of Adults with Moderate-to-Severe Active Ulcerative Colitis: An Evidence Review Group Perspective of a NICE Single Technology Appraisal.

As part of its single technology appraisal (STA) process, the National Institute for Health and Care Excellence (NICE) invited the manufacturer of vedolizumab (Takeda UK) to submit evidence of the clinical effectiveness and cost effectiveness of vedolizumab for the treatment of patients with moderate-to-severe active ulcerative colitis (UC). The Evidence Review Group (ERG) produced a critical review of the evidence for the clinical effectiveness and cost effectiveness of the technology, based upon the company's submission to NICE. The evidence was derived mainly from GEMINI 1, a Phase 3, multicentre, randomised, double-blinded, placebo-controlled study of the induction and maintenance of clinical response and remission by vedolizumab (MLN0002) in patients with moderate-to-severe active UC with an inadequate response to, loss of response to or intolerance of conventional therapy or anti-tumour necrosis factor (TNF)-α. The clinical evidence showed that vedolizumab performed significantly better than placebo in both the induction and maintenance phases. In the post hoc subgroup analyses in patients with or without prior anti-TNF-α therapy, vedolizumab performed better then placebo (p value not reported). In addition, a greater improvement in health-related quality of life was observed in patients treated with vedolizumab, and the frequency and types of adverse events were similar in the vedolizumab and placebo groups, but the evidence was limited to short-term follow-up. There were a number of limitations and uncertainties in the clinical evidence base, which warrants caution in its interpretation-in particular, the post hoc subgroup analyses and high dropout rates in the maintenance phase of GEMINI 1. The company also presented a network meta-analysis of vedolizumab versus other biologic therapies indicated for moderate-to-severe UC. However, the ERG considered that the results presented may have underestimated the uncertainty in treatment effects, since fixed-effects models were used, despite clear evidence of heterogeneity among the trials included in the network. Results from the company's economic evaluation (which included price reductions to reflect the proposed patient access scheme for vedolizumab) suggested that vedolizumab is the most effective option compared with surgery and conventional therapy in the following three populations: (1) a mixed intention-to-treat population, including patients who have previously received anti-TNF-α therapy and those who are anti-TNF-α naïve; (2) patients who are anti-TNF-α naïve only; and (3) patients who have previously failed anti-TNF-α therapy only. The ERG concluded that the results of the company's economic evaluation could not be considered robust, because of errors in model implementation, omission of relevant comparators, deviations from the NICE reference case and questionable model assumptions. The ERG amended the company's model and demonstrated that vedolizumab is expected to be dominated by surgery in all three populations

Cambogin Is Preferentially Cytotoxic to Cells Expressing PDGFR

Platelet-derived growth factor receptors (PDGFRs) have been implicated in a wide array of human malignancies, including medulloblastoma (MB), the most common brain tumor of childhood. Although significant progress in MB biology and therapeutics has been achieved during the past decades, MB remains a horrible challenge to the physicians and researchers. Therefore, novel inhibitors targeting PDGFR signaling pathway may offer great promise for the treatment of MB. In the present study, we investigated the cytotoxicity and mechanisms of cambogin in Daoy MB cells. Our results show that cambogin triggers significant S phase cell cycle arrest and apoptosis via down regulation of cyclin A and E, and activation of caspases. More importantly, further mechanistic studies demonstrated that cambogin inhibits PDGFR signaling in Daoy and genetically defined mouse embryo fibroblast (MEF) cell lines. These results suggest that cambogin is preferentially cytotoxic to cells expressing PDGFR. Our findings may provide a novel approach by targeting PDGFR signaling against MB

Pirfenidone for Treating Idiopathic Pulmonary Fibrosis: An Evidence Review Group Perspective of a NICE Single Technology Appraisal

The National Institute for Health and Care Excellence (NICE) published guidance on the use of pirfenidone (Esbriet®, Roche) for the treatment of mild to moderate idiopathic pulmonary fibrosis (IPF) in 2013. NICE decided to review existing guidance following publication of an additional clinical trial, and invited the manufacturer of pirfenidone to submit evidence of its clinical and cost effectiveness for the treatment of mild to moderate IPF when compared with best supportive care (BSC) or nintedanib; nintedanib was a comparator only for moderate IPF. An independent Evidence Review Group (ERG) critiqued the company submission and this paper summarises their report and subsequent NICE guidance. The key clinical effectiveness evidence was based on three randomised controlled trials (RCTs) and an open-label extension study. Supportive data were provided from two additional RCTs conducted in Japan, while one additional open-label study was included for safety outcomes. Meta-analysis of the three key RCTs found pirfenidone to be effective at reducing disease progression compared with placebo, but statistically significant differences were not identified in all of the RCTs. A statistically significant reduction in all-cause mortality was only demonstrated when pooling data across studies. The treatment effects of pirfenidone and nintedanib were broadly similar, based on an indirect comparison using network meta-analysis, although they have slightly different adverse event profiles. There remains considerable uncertainty in the cost-effectiveness estimates for pirfenidone versus BSC, particularly due to uncertainty regarding the duration of treatment effect and the method used to implement the stopping rule within the economic model